Anti-Epileptics Flashcards
Classification of seizure types
- Focal
- Generalize
Epilepsy: etiology
- Structural (neurologic defect)
- Genetic
- Infectious
- Immune
- Metabolism
How is a seizure different from epilepsy
- Seizure is an isolated incidents
- 2 or more = epilsepsy
(certain drugs can cause a seizure, that doesn’t make an epilepsy diagnosis)
Focal seizure types
- Simple partial
- Complex partial
- Secondarily generalized (focal in one location → spreads to another part of the brain)
Generalized seizure types (5)
- Absence (petit mal - 15 sec)
- Atonic
- Tonic
- Tonic-clonic
- Myoclonic
Define myoclonic seizure
- Synchronous jerks
- Bilateral
Tonic clonic seizure characteristics
Convulsive seizure (aka Grand mal)
Atonic seizure
Fall to the ground
Choosing anti-epileptic drugs involves which factors (4)?
- Advanced Age, gender
- Epilepsy syndrome
- Related medical conditions (HIV- HAART therapy)
- Seizure type
(and … Efficacy, Side effects, Pharmacokinetics (may lead to toxicity)
Mono-therapy should be used until seizures are controlled or toxicity occurs.
If mono-therapy has reduced, but not eliminated seizures, what do you do?
Add another drug to the regimen rather than switching to a new drug
(caution: drug interaction and pregnancy!!)
Why can’t you just remove a drug from the patient’s regimen?
Tapering, otherwise → rebound seizures
Neuronal mechanism underlying seizures (3)
- Suppression of GABA (inhibitory)
- Increase in Ca2+ influx via T-Type Ca2+ channels in thalamic neurons
- Glutamate → activation of excitatory NTs
(spiklet causes the shift that leads to siezure→ stimulates other parts of the brain)
Adverse effects of anti-seizure drugs
- Suicide
- Multi-organ hypersensitivity reactions (can be fatal)
(certain populations are more sensitive)
Action potential mechanism of action
Antiepileptic drugs: 3 MOAs
Phenytoin:
- MOA
- Indications
- Blocks voltage-gated sodium channels
- Focal seizures, Tonic-clonic seizures, Status epilepticus
Limitations of use for phenytoin
Metabolized by the liver under polygenic control which varies between patients
Define dose-dependent kinetics
- Lower concentrations are eliminated by first order kinetics
- Higher concentrations saturate biotransformation enzymes and inhibit zero order kinetics
Phenytoin interaction induces which enzyme systems?
- CYP2C
- CYP3A
- UGT
(pronounced “sip-2-C”; This accelerates metabolism of other drugs)
Phenytoin side effects (5)
- Nystagmus and ataxia in elderly
- Gingival hyperplasia
- Neuropathy and osteoporosis (long term use)
- Interferes with folate metabolism (megaloblastic anemia & fetal hydantoin syndrome)
- SJS & TEN linked to polymorphism in HLA allele (small population)
Carbamazepine and oxcarbazepine indications
Focal seizures and generalized tonic-clonic seizures
Carbamazepine and oxcarbazepine mechanism of action
Inhibits generation of repetitive action potentials in the epileptic focus and prevents their spread
(activates its own metabolism)
Oxcarbazepine has a lower risk for ________, but a higher risk for ______.
- Lower risk for p450 enzymes inducer → Lower risk of rash
- Hyponatremia
Oxcarbazepine is converted to ______
Active metabolite
(blocks sodium channel and thought to modulate calcium channels)
Carbamazepine & Oxcarbazepine pharmacokinetics
- active metabolite: carbamazepine epoxide induces its own metabolism and that of other drugs
- Inducer of CYP & UDP enzymes
Lamotrigine MOA
Block sodium Channel and l-type calcium channels
Dosages of _____ should be reduced when adding to valproate therapy to reduce risk of SJS.
Lamotragine
Valproic acid mechanism of action
Block sodium and T-Type calcium channels
Valproic acid indications
- Mixed seizure types
- Absence seizure that does not respond to ethosuximide
- alternative to phenytoin and carbamazepine for focal seizures
(2nd line)
Valproic acid side effects (6)
- GI: transient anorexia, N/V
- Teratogenic effects
- Hyperammonia
- Hypersensitivity
- Inhibits metabolism of other drugs
- Hepatotoxicity
(high risk for congenital malformation for pregnant women)
Ezogabine MOA
Opens potassium channels and stabilizes rester membrane potential to hyperpolarize the neuron
Ezogabine uses
Treatment of seizures in children and adults with LGS
Ezogabine side effects
- Blue skin discoloration
- Urinary retention
- Retinal abnormalities
______ reduces propagation of abnormal electrical activity by inhibiting T-Type calcium channels
Ethosuximide
Ethosuximide side effects (3)
- Dizziness
- Nausea
- Epigastric discomfort
Ethosuximide interactions
- Valproate inhibits metabolism
- Haloperidol can alter seizure pattern
Ethosuximide indications
absence seizures
(long half life 30 hours in children, 55 in adults)
Gabapentin MOA (2)
- ⇡ release of GABA
- inhibits L-type Ca2+ channels (⇣ NT release)
(Analog of GABA; adjunct therapy for focal seizures; does NOT mimic GABA, acts at the channel)
Vigabatrin MOA
Inhibits GABA metabolism
(gamma aminobutyric acid transaminase (GABA-T))
Vigabatrin use
focal epilepsy
Vigabatrin side effect
visual field loss
Benzodiazepine MOA (2)
- Increases affinity of GABA for receptor
- enhances Cl- flux
(reserved for Emergent tx)
Benzodiazepine is an adjunct treatment for :
focal & tonic-clonic seizures
(reserved for emergency or acute seizure due to tolerance)
Benzodiazepines adverse effects (3)
- Dizziness
- Ataxia
- Drowsiness
Which 2 benzodiazepine can be used for treating lennox-gastaut syndrome?
Clobazam & clonazepam
Phenobarbital MOA (2)
- Enhances the inhibitory effects of GABA- mediated neurons
- Binds to allosteric sites
(second line focal seizures & tonic-clonic seizures)
Primidone is metabolized into _____ & _____.
- phenobarbitol
- phenylethylmalonamide
(Both have anticonvulsant activity & block sodium channels and potentiate GABA)
Hypersensitivity to barbiturates will develop as a
Rash
Felbamate MOA
Blocking coactivation of the nmda receptor
Felbamate indication
Partial seizures refractory to other drugs do to risk of aplastic anemia and hepatic failure
Felbamate is an inhibitor of drugs metabolized by _____
- CYP2C19
- CYP3A4
Rufinamide interactions
- induced by carbamazepine and phenytoin
- valproate inhibits
Topiramate adverse effects
- cleft palate
- somnolence
- ataxia
- weight loss
- paresthesias
Topiramate MOA
Blocks voltage-dependent sodium channels, glutamate receptors and augmentation of GABA
Topiramate indications
Focal and primary generalized epilepsy
(Olek says myoclonic as well)
Define status epilepticus
- Two or more seizures occur without fully recovering Consciousness in between episodes
- Life-threatening emergency: prolonged hypoxia→ severe brain damage
Status epilepticus treatment
- Benzodiazepine followed by a slow-acting medication (phenytoin)
- phenobarbital if others fail
________ (2) prefered rx for status epilepticus
- lorazapam
- diazepam
Anti-epileptic medication contraindicated in pregnancy (2)
- Divalproex
- Barbiturates
- Phenytoin
- carbamazepine
- lamotrigine
- topiramate
- valproate (sometimes used if no other option)
Rufinamide MOA
inhibits Na channels → inhibits mGluR5 (subset of glutamate receptors)
(inhibitos CYp2E1 & CYP3A4)
Which meds treat tonic-clonic & partial seizures?
- Carbamazepine
- Phenytoin
- Valproate
Which drug treats absence seizures in adults & which for children?
- adults: valproate
- children: ethosuximide
Which drug treats myoclonic & atonic seizures?
valproate
Which drugs treat status epilepticus?
- lorazepam
- diazepam
- phenytoina
Lacosamide MOA
blocks voltage-gated Na+
Lacosamide is indicated for _______ seizures
focal
Dizziness, headache and fatigue are the adverse effects of which drug that treats focal seizures?
Lacosamide
Dravet syndrome tx
stirpentol (GABA NT)
(more drug interactions)
